In a presentation at the American Association of Pharmaceutical Scientists (AAPS) PharmaSci 360 conference, Dr. Nitin Rathore, Director of Process Development at Amgen, detailed the company’s business and operational assessment of two next-generation aseptic filling systems. Both systems are installed at Amgen’s Thousand Oaks, California facility, one of them being the SA25 aseptic filling workcell from Cytiva.

When considering next generation bioprocessing technologies Dr. Rathore knows one of the key questions that is asked by process engineers and plant managers – “is this technology good enough to give me the process performance?” The concern being that novel technology can sometimes force compromises due to process changes.

Assessing next-generation filling systems for operational and business needs

The assessment was to determine how the filling systems could help Amgen succeed in an environment of high-mix, low-volume manufacturing. In this model, Amgen would be making a greater number of products focused on smaller patient populations.

From a business perspective, filling technologies need to be less costly, and enable the company to match production to the forecast with a smaller margin of error. The technologies would support a scale-out model of adding capacity quickly when needed.

From an operational perspective, new aseptic filling technologies need to require less space, have the flexibility for different dosage formats, and changeover and decontaminate quickly. They need to support more rapid technology transfer and eliminate required cleaning infrastructure.

Amgen’s assessment of the SA25 aseptic filling workcell

Dr. Rathore began his comments by saying the SA25 is a “very elegant design”, and the development of a gloveless isolator represented a “paradigm shift.” Amgen’s operational assessment rated the machine’s capacity at two million units annually, and the machine needed only two operators. He singled out the machine’s changeover and decontamination times as significant improvements versus past filling machinery and barrier systems. The SA25 was also called “adaptable” for its ability to fill different dosage formats.

Amgen’s assessment of the SA25 concluded that the machine was aligned with its process performance requirements, with data shown to support various criteria.

Since gloveless robotic isolators differ from past filling machinery, it was identified that adoption of the SA25 would require proactive communication with regulators. Cytiva is coordinating this effort through its User Group, with both Cytiva and customers generating and sharing data to support regulatory submissions.

Dr. Rathore also said that optimization was needed on lyophilization cycles for vials that remain in ready-to-use nests in combination with nested press-fit closures. He did note that nested closures did not pose additional resistance to vapour flow during lyo cycles. Differences between nest configurations provided by different vial manufacturers did however create differences in heat transfer and cycle times, especially where vials did or did not make direct contact with the lyophilizer’s shelves.

The presentation concluded by linking different filling solutions to business cases. Dr. Rathore said that there are equally valid business cases for conventional high-speed machines focused on a single container and for small-scale flexible fillers like those offered by Cytiva.

Key lessons from the implementation of a gloveless robotic isolator

  • Process performance is not compromised by this novel technology, sterility assurance is more easily achieved
  • The machine met the requirement for flexible capacity since the future of a drug product is uncertain with unknown clinical and market demands

The key to implementing next generation bioprocessing technologies is to understand business needs and then assess suitable solutions, ideally with today’s technology. In the case of Amgen, the SA25 aseptic filling workcell met business and operational needs, along with providing additional benefits with its next generation technology.

"Benefit-wise it is very clear you can reduce the capital burden and you can have significant footprint reduction associated with these technologies."
- Dr. Nitin Rathore, Director of Process Development, Amgen